PROJECT SUMMARY/ABSTRACT The use of genetically modified mice has greatly expanded our understanding of kidney development, genetics, physiology, and pathophysiology. The UT Southwestern O'Brien Center Animal Models Core (Core A) has served the community for 10 years and will continue to provide cutting edge technology to investigators wishing to generate mouse models for the study of kidney function and disease. The core will serve multiple purposes. We provide the necessary reagents and expertise to mouse geneticists who do not normally work with the kidney to facilitate and encourage their move into this field. We encourage investigator who do not normally use mouse models, including and especially clinical investigators, to venture into the mouse system and to ease this transition. We will also assist the generation of non-genetic models of acute and chronic kidney disease to assist investigators in their studies. We will accomplish our objectives in several ways. First, the core has generated and will distribute many kidney-specific conditional (inducible activator and repressor lines), glomerular or tubule segment-specific Cre recombinase lines to be crossed to floxed or tet responder lines of interest to the investigator. We will provide advice as well as the actual mousselines. Second, core personnel will assist in the generation of additional transgenic mice, knockout/in mice and cell lines as required by co-investigators. We will either offer advice or if the demand is high, we plan to add a new line t our Core once a year. Finally, core personnel will perform for or train investigators in the use of various models of organ injury/repair as well as ex vivo culture. We will always have exploratory modules where we participate in the cutting edge of technologies in renal research. We have developed technologies for 4-D live imaging of kidneys, metabolite labeling and quantification in organ culture, metabolomics in organ culture, CRISPR-Cas9 mediated genome engineering, isolation, expansion and differentiation of nephron progenitor cells. The ultimate purpose of this core is to facilitate research on kidney development, genetics, physiology and pathophysiology.